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含口蹄疫免疫优势肽的实验设计纳米脂质体疫苗的免疫评价。

Immunity Evaluation of an Experimental Designed Nanoliposomal Vaccine Containing FMDV Immunodominant Peptides.

机构信息

Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University of Tehran, Iran.

出版信息

Arch Razi Inst. 2021 Nov 30;76(5):1183-1190. doi: 10.22092/ari.2021.352498.1566. eCollection 2021 Nov.

Abstract

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals. The particular virus causing FMD disease is called FMD virus and is a member of the Aphthovirus genus in the Picornaviridae family. The FMD virus has an 8500 nt long single strain positive RNA genome with one open reading frame (ORF) trapped in an icosahedral capsid protein. This virus genome doesn't have proofreading property which leads to high mutagenesis. It has seven serotypes, including O, A, ASIA, SAT1, SAT2, and C serotypes, as well as many subtypes. Iran is an endemic region for foot-and-mouth disease. Vaccination of susceptible animals with an inactivated whole-virus vaccine is the only way to control the epidemic in many developing countries. Today, conventionally attenuated and killed virus vaccines are being used worldwide. In Iran, animals have been vaccinated every 105 days with an inactivated FMD vaccine. Although commercially available FMD vaccines are effective, they provide short-term immunity requiring regular boosters. A new FMD vaccine is needed to improve immunization, safety, and long-term immune responses. A synthetic peptide vaccine is one of the safe and important vaccines. Peptide vaccine has low immunogenicity, requiring strong adjuvants. Nanoliposomes can be used as new adjuvants to improve immune response. In the current study, nanoliposomal carriers were selected using Dimyristoylphosphatidylcholine (DMPC), dimyristoyl phosphoglycerol (DMPG), and Cholesterol (Chol) as an adjuvant containing two immunodominant synthetic FMDV peptides. The liposomal formulations were characterized by various physicochemical properties. The size, zeta potential, and encapsulation efficiency were optimized, and the obtained nanoliposome was suitable as a vaccine. The efficacy of vaccines has been evaluated in guinea pigs as animal models. Indirect ELISA was used to detect FMDV-specific IgG. The obtained results indicated that although antibody titer was observed, the amount was lower compared to the groups that received inactivated virus-containing liposomes. In addition, the results showed that liposome was an appropriate adjuvant, compared to other adjuvants, such as Alum and Freund, and can act as a depot and induce an immune response.

摘要

口蹄疫(FMD)是一种高度传染性的病毒性疾病,影响偶蹄类动物。导致 FMD 疾病的特定病毒称为口蹄疫病毒,是小核糖核酸病毒科口疮病毒属的一员。口蹄疫病毒具有 8500 个核苷酸长的单株正链 RNA 基因组,被包裹在一个二十面体衣壳蛋白内。这种病毒基因组没有校对功能,导致高度突变。它有 7 种血清型,包括 O、A、ASIA、SAT1、SAT2 和 C 血清型,以及许多亚型。伊朗是口蹄疫的地方性流行地区。在许多发展中国家,用灭活全病毒疫苗对易感动物进行免疫接种是控制疫情的唯一方法。如今,常规减毒和灭活病毒疫苗在全球范围内使用。在伊朗,动物每 105 天用灭活口蹄疫疫苗接种一次。虽然市售的口蹄疫疫苗是有效的,但它们提供的是短期免疫,需要定期加强。需要一种新的口蹄疫疫苗来改善免疫接种、安全性和长期免疫反应。合成肽疫苗是一种安全且重要的疫苗。肽疫苗的免疫原性低,需要使用强佐剂。纳米脂质体可以作为新的佐剂来提高免疫反应。在本研究中,使用二肉豆蔻酰磷脂酰胆碱(DMPC)、二肉豆蔻酰磷脂酰甘油(DMPG)和胆固醇(Chol)作为佐剂,选择了纳米脂质体载体,其中包含两种免疫优势的合成口蹄疫病毒肽。对脂质体配方进行了各种理化性质的表征。优化了粒径、Zeta 电位和包封效率,得到的纳米脂质体适合作为疫苗。以豚鼠为动物模型评价了疫苗的功效。间接 ELISA 用于检测口蹄疫病毒特异性 IgG。结果表明,尽管观察到了抗体滴度,但与接受含灭活病毒的脂质体的组相比,数量较低。此外,结果表明,与其他佐剂如明矾和福氏佐剂相比,脂质体是一种合适的佐剂,可作为储存库并诱导免疫反应。

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